Field of the Invention
The invention generally relates to compositions and methods for treating victims of carbon monoxide and/or cyanide poisoning. In particular, the compositions comprise reduced forms of Vitamin B12 such as hydroxocobalamin or cobinamide to treat victims of carbon monoxide and/or cyanide poisoning (such as victims of smoke inhalation).
Background of the Invention
Carbon monoxide (CO) exposure is the leading cause of unintentional poisoning death and long-term morbidity in the US. In 2012 alone, there were over 13,000 cases reported to US poison centers, with 143 serious outcomes and 54 deaths1. However serious delayed sequelae such as persistent and recurrent neurological deficits may occur in up to 30% of patients following apparent recovery from acute symptoms; these delayed neurological complications (DNS) may not become evident until weeks or months after exposure2. Reduction in O2 delivery to the tissues is thought to result from binding of CO to hemoglobin (Hgb) to form carboxyhemoglobin (COHgb). Carbon monoxide binds with Hgb with an affinity that is 200-250 times greater than oxygen, thus rendering the concentration of oxyhemoglobin lower in patients with CO exposure. In addition the binding of carbon monoxide to Hgb results in conformational changes in Hgb that reduces its ability to offload its remaining O2 to the tissues and subsequently causing hypoxic injury. As a result, current acute-care management involves either normobaric (NBO) or hyperbaric (HBO) oxygen therapy; however, the efficacy of oxygen therapy for prevention of DNS specifically is uncertain and has not been evaluated systematically3. Further limitations of oxygen therapy include unpredictable availability of equipment and delays between point of exposure, recognition of signs and symptoms, and initiation of therapy4. No antidotes for CO toxicity currently exist.
Victims of smoke inhalation typically suffer from exposure to both CO and cyanide (polyintoxication). While hydroxocobalamin has been used to treat cyanide poisoning and smoke inhalation for over 40 years, the form that has been used to date is effective in scavenging only cyanide; CO exposure must be treated using O2 as described above.
To be clinically useful, proposed antidotes for CO toxicity must be readily available, field-deployable, targeted, rapidly effective, and safe. Thus, what is needed are efficacious compositions and methods of treating CO poisoning, and for treating CO and cyanide poisoning together using a single formulation.